The center will continue to support research in basic adaptive mechanisms of the brain's neurotransmitter biosynthetic systems and receptors to drugs of abuse including opiates, hallucinogens, stimulants, sedatives, cocaine, some psychotherapeutic agents, and alcohol. The mechanisms under study include receptor sensitivity, uptake of amino acid precursors into nerve endings, nerve ending biosynthetic enzyme activity, nerve ending biosynthetic enzyme synthesis, degradation, and axoplasmic flow. Behavioral correlates of macromolecular changes induced by drugs will be monitored. Enzymes under study include tyrosine hydroxylas, tryptophan hydroxylase, tryptophan hydroxylase, choline acetyltransferase, and glutamic acid decarboxylase. Behavioral studies involving intraventricular self-administration of opiates and stimulants will be correlated with changes in the above noted measures. Under development is an integrated model for macromolecular adaptation in neurotransmitter systems in the brain to drugs of abuse.